Lipid-Core Plaque Assessed by Near-Infrared Spectroscopy and Procedure Related Microvascular Injury

BACKGROUND AND OBJECTIVES@#Microvascular damage due to distal embolization during percutaneous coronary intervention (PCI) is an important cause of periprocedural myocardial infarction. We assessed the lipid-core plaque using near-infrared spectroscopy (NIRS) and microvascular dysfunction invasively with the index of microcirculatory resistance (IMR) and evaluated their relationship.@*METHODS@#This study is pilot retrospective observational study. We analyzed 39 patients who performed NIRS before and after PCI, while fractional flow reserve, thermo-dilution coronary flow reserve (CFR) and IMR were measured after PCI. The maximum value of lipid core burden index (LCBI) for any of the 4-mm segments at the culprit lesion (culprit LCBI(4mm)) was calculated at the culprit lesion. We divided the patients into 2 groups using a cutoff of culprit LCBI(4mm) ≥500.@*RESULTS@#Mean pre-PCI LCBI was 333±196 and mean post-PCI IMR was 20±14 U. Post-PCI IMR was higher (15.6±7.3 vs. 42.6±17.6 U, p<0.001) and post-PCI CFR was lower (3.7±2.2 vs. 2.1±1.0, p=0.029) in the high LCBI group. Pre-PCI LCBI was positively correlated with post-PCI IMR (ρ=0.358, p=0.025) and negatively correlated with post-PCI CFR (ρ=−0.494, p=0.001). The incidence of microvascular dysfunction (IMR ≥25 U) was higher in the high LCBI group (9.4% vs. 85.7%, p<0.001). However, there were no significant differences in the incidences of creatine Kinase-MB (9.4% vs. 14.3%, p=0.563) and troponin-I elevation (12.5% vs. 14.3%, p=1.000).@*CONCLUSIONS@#A large lipid-core plaque at the ‘culprit’ lesion is observed higher incidence of post-PCI microvascular dysfunction after PCI. Prospective study with adequate subject numbers will be needed.

Lipid-Core Plaque Assessed by Near-Infrared Spectroscopy and Procedure Related Microvascular Injury

BACKGROUND AND OBJECTIVES: Microvascular damage due to distal embolization during percutaneous coronary intervention (PCI) is an important cause of periprocedural myocardial infarction. We assessed the lipid-core plaque using near-infrared spectroscopy (NIRS) and microvascular dysfunction invasively with the index of microcirculatory resistance (IMR) and evaluated their relationship. METHODS: This study is pilot retrospective observational study. We analyzed 39 patients who performed NIRS before and after PCI, while fractional flow reserve, thermo-dilution coronary flow reserve (CFR) and IMR were measured after PCI. The maximum value of lipid core burden index (LCBI) for any of the 4-mm segments at the culprit lesion (culprit LCBI(4mm)) was calculated at the culprit lesion. We divided the patients into 2 groups using a cutoff of culprit LCBI(4mm) ≥500. RESULTS: Mean pre-PCI LCBI was 333±196 and mean post-PCI IMR was 20±14 U. Post-PCI IMR was higher (15.6±7.3 vs. 42.6±17.6 U, p<0.001) and post-PCI CFR was lower (3.7±2.2 vs. 2.1±1.0, p=0.029) in the high LCBI group. Pre-PCI LCBI was positively correlated with post-PCI IMR (ρ=0.358, p=0.025) and negatively correlated with post-PCI CFR (ρ=−0.494, p=0.001). The incidence of microvascular dysfunction (IMR ≥25 U) was higher in the high LCBI group (9.4% vs. 85.7%, p<0.001). However, there were no significant differences in the incidences of creatine Kinase-MB (9.4% vs. 14.3%, p=0.563) and troponin-I elevation (12.5% vs. 14.3%, p=1.000). CONCLUSIONS: A large lipid-core plaque at the ‘culprit’ lesion is observed higher incidence of post-PCI microvascular dysfunction after PCI. Prospective study with adequate subject numbers will be needed.

Ischemia-based Coronary Revascularization: Beyond Anatomy and Fractional Flow Reserve

Treatment strategies for patients with coronary artery disease (CAD) should be based on objective evidence of inducible ischemia in the subtended myocardium to improve clinical outcomes, symptoms, and cost-effectiveness. Fractional flow reserve (FFR) is the most verified index to-date for invasively evaluating lesion-specific myocardial ischemia. Favorable results from large clinical trials that applied FFR-guided percutaneous coronary intervention (PCI) prompted changes in coronary revascularization guidelines to emphasize the importance of this ischemia-based strategy using invasive coronary physiology. However, the frequency of functional evaluations is lacking in daily practice, and visual assessment still dominates treatment decisions in CAD patients. Despite recent efforts to integrate functional and anatomical assessments for coronary stenosis, there is considerable discordance between the 2 modalities, and the diagnostic accuracy of simple parameters obtained from current imaging tools is not satisfactory to determine functional significance. Although evidence that supports or justifies anatomy-guided PCI is more limited, and FFR-guided PCI is currently recommended, it is important to be aware of conditions and factors that influence FFR for accurate interpretation and application. In this article, we review the limitations of the current anatomy-derived evaluation of the functional significance of coronary stenosis, detail considerations for the clinical utility of FFR, and discuss the importance of an integrated physiologic approach to determine treatment strategies for CAD patients.

Longitudinal Stent-Strut Injury at the Distal End of a Newer-generation Drug-eluting Stent

No abstract available.

Extrinsic Compression of the Left Main Coronary Artery by a Huge Aortic Arch Aneurysm Mimicking Acute Coronary Syndrome

No abstract available.

Ischemia-based Coronary Revascularization: Beyond Anatomy and Fractional Flow Reserve

Treatment strategies for patients with coronary artery disease (CAD) should be based on objective evidence of inducible ischemia in the subtended myocardium to improve clinical outcomes, symptoms, and cost-effectiveness. Fractional flow reserve (FFR) is the most verified index to-date for invasively evaluating lesion-specific myocardial ischemia. Favorable results from large clinical trials that applied FFR-guided percutaneous coronary intervention (PCI) prompted changes in coronary revascularization guidelines to emphasize the importance of this ischemia-based strategy using invasive coronary physiology. However, the frequency of functional evaluations is lacking in daily practice, and visual assessment still dominates treatment decisions in CAD patients. Despite recent efforts to integrate functional and anatomical assessments for coronary stenosis, there is considerable discordance between the 2 modalities, and the diagnostic accuracy of simple parameters obtained from current imaging tools is not satisfactory to determine functional significance. Although evidence that supports or justifies anatomy-guided PCI is more limited, and FFR-guided PCI is currently recommended, it is important to be aware of conditions and factors that influence FFR for accurate interpretation and application. In this article, we review the limitations of the current anatomy-derived evaluation of the functional significance of coronary stenosis, detail considerations for the clinical utility of FFR, and discuss the importance of an integrated physiologic approach to determine treatment strategies for CAD patients.

Bioresorbable Vascular Scaffold Korean Expert Panel Report

Bioresorbable vascular scaffold (BRS) is an innovative device that provides structural support and drug release to prevent early recoil or restenosis, and then degrades into nontoxic compounds to avoid late complications related with metallic drug-eluting stents (DESs). BRS has several putative advantages. However, recent randomized trials and registry studies raised clinical concerns about the safety and efficacy of first generation BRS. In addition, the general guidance for the optimal practice with BRS has not been suggested due to limited long-term clinical data in Korea. To address the safety and efficacy of BRS, we reviewed the clinical evidence of BRS implantation, and suggested the appropriate criteria for patient and lesion selection, scaffold implantation technique, and management.

Clinical and Angiographic Outcomes of the First Korean-made Sirolimus-Eluting Coronary Stent with Abluminal Bioresorbable Polymer

BACKGROUND AND OBJECTIVES: This trial evaluated the safety and efficacy of the Genoss drug-eluting coronary stent. METHODS: This study was a prospective, multicenter, randomized trial with a 1:1 ratio of Genoss drug-eluting stent (DES)™ and Promus Element™. Inclusion criteria were the presence of stable angina, unstable angina, or silent ischemia. Angiographic inclusion criteria were de novo coronary stenotic lesion with diameter stenosis >50%, reference vessel diameter of 2.5–4.0 mm, and lesion length ≤40 mm. The primary endpoint was in-stent late lumen loss at 9-month quantitative coronary angiography follow-up. Secondary endpoints were in-segment late lumen loss, binary restenosis rate, death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis during 9 months of follow-up. RESULTS: We enrolled 38 patients for the Genoss DES™ group and 39 patients for the Promus Element™ group. In-stent late lumen loss at 9 months was not significantly different between the 2 groups (0.11±0.25 vs. 0.16±0.43 mm, p=0.567). There was no MI or stent thrombosis in either group. The rates of death (2.6% vs. 0%, p=0.494), TLR (2.6% vs. 2.6%, p=1.000), and TVR (7.9% vs. 2.6%, p=0.358) at 9 months were not significantly different. CONCLUSION: This first-in-patient study of the Genoss DES™ stent showed excellent angiographic outcomes for in-stent late lumen loss and major adverse cardiac events over a 9-month follow-up.

Clinical Outcomes in Patients with Deferred Coronary Lesions according to Disease Severity Assessed by Fractional Flow Reserve

Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86–0.95 (n = 330), group 3: 0.81–0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1–4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank P = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; P = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; P = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; P = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary.

Anatomical Discrepancy Between The Coronary Sinus and the Mitral Annulus by Fluoroscopy

BACKGROUND AND OBJECTIVES: Intracardiac electrocardiograms (ECGs) from the coronary sinus (CS) provide important information for identifying a left-sided bypass tract. However, a previous study revealed an anatomical discrepancy between the CS and mitral annulus (MA) in cadaver hearts. The purpose of this study was to evaluate the anatomical relationship between the CS and MA in the living body by using fluoroscopy. SUBJECTS AND METHODS: We analyzed patients who had an ablation for 42 left-sided bypass tracts and one paroxysmal atrial fibrillation. A left atriogram was performed during the ablation by using a pigtail catheter via the transseptal approach. The distances between the CS and MA were measured at 30° right anterior oblique (RAO) and 60° left anterior oblique (LAO) projections at the end of ventricular systole and diastole. RESULTS: The distances between the CS and MA at the RAO projection were 9.74±3.50, 3.86±2.58, and 9.02±6.04 mm during systole and 12.89±5.59, 3.97±3.24, and 10.71±4.12 mm during diastole at the proximal, middle, and distal CS, respectively. The distances between the CS and MA at the LAO projection were 6.84±2.77, 1.80±1.51, and 4.57±3.24 mm during systole and 9.91±3.25, 4.21±3.59, and 7.02±3.12 mm during diastole at the proximal, middle, and distal CS, respectively. CONCLUSION: An anatomical discrepancy was detected between the CS and MA in most cases. Therefore, intracardiac ECGs of the CS cannot exactly localize left-sided bypass tracts.

Time Variance of Electrocardiographic Transmural Dispersion in Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: The mechanism responsible for lethal ventricular arrhythmia (LVA) after acute myocardial infarction (AMI) remains unclear. SUBJECTS AND METHODS: The corrected QT interval (QTc) and interval from the peak to the end of the T wave (TpTe) were measured, which indicated myocardial transmural dispersion of repolarization (TDR) in 72 patients with AMI. TpTe was also expressed as a corrected value, [TpTe/QTe]x100% and TpTe/√RR. These parameters were obtained from all the 12-leads of electrocardiography after arrival at the hospital, just before and after percutaneous coronary intervention (PCI), and at 4, 24, and 48 hours and 5 days after PCI. RESULTS: Analyzing with repeated measures analysis of variance, the TpTe, [TpTe/QTe]x100% and TpTe/√RR after AMI showed significant changes in time variance. The patients were divided into LVA (17 patients, 24%) and non-LVA group (55 patients, 76%). The [TpTe/ QTe]×100% (V₂: 25±7% vs. 22±5%, p=0.036) and TpTe/√RR (V₂: 109 ± 42 ms vs. 88 ± 22 ms, p=0.05, V₃: 108±39 ms vs. 91±27 ms, p=0.048) in V₂ and V₃ leads were prolonged in the LVA group after PCI. The [TpTe/QTe]×100% (28±9 % vs. 22±5%, p=0.025) and TpTe/√RR (129±53 ms vs. 99±41 ms, p=0.05) in V₃ lead were prolonged in the LVA group 24 hours after PCI. CONCLUSION: The mechanisms responsible for LVA after AMI may be associated with increased TDR, and PCI may have an important role in reducing LVA.

Angiographic spontaneous pseudo-resolution of a coronary artery aneurysm after implantation of a sirolimus-eluting stent

No abstract available.

Recurrent Stent Thrombosis in a Patient with Antiphospholipid Syndrome and Dual Anti-Platelet Therapy Non-Responsiveness

Antiphospholipid syndrome (APS), the most common acquired hypercoagulable condition, is diagnosed by persistent presence of antiphospholipid antibodies and episodes of vascular thrombosis. It may be an important predisposing factor for stent thrombosis, resulting in poor outcomes. Also, anti-platelet therapy non-responsiveness is associated with stent thrombosis. We report a case of a 39-year-old man who after undergoing successful percutaneous coronary intervention for significant coronary artery disease suffered repeated stent thrombosis events leading to ST-segment elevation myocardial infarction. Eventually, he underwent coronary artery bypass surgery because of uncontrolled thrombosis and was diagnosed as having APS and dual antiplatelet therapy non-responsiveness.

Usefulness of Hyperemic Microvascular Resistance Index as a Predictor of Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction

BACKGROUND AND OBJECTIVES: Microvascular function is a useful predictor of left ventricular functional changes in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated the usefulness of the hyperemic microvascular resistance index (hMVRI) for predicting long-term major adverse cardiovascular events (MACEs) in patients with STEMI assessed immediately after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: hMVRI were evaluated in 145 patients with first acute STEMI treated with primary PCI using an intracoronary Doppler wire. hMVRI was defined as the ratio of mean aortic pressure over hyperemic averaged peak velocity of infarct-related artery. Major adverse cardiovascular events (MACEs) included cardiac death and re-hospitalization for congestive heart failure. RESULTS: During the mean follow-up of 85+/-43 months, MACEs occurred in 17.2% of patients. Using a receiver-operating characteristics analysis, hMVRI >2.82 mm Hg.cm-1.sec (sensitivity: 87%; specificity: 69%; and area under curve: 0.818) was the best cut-off values for predicting future cardiac events. The Cox proportional hazard analysis showed that hMVRI was an independent predictor for long-term MACEs (hazard ratio 1.741, 95% confidence interval 1.348-2.264, p2.82 mm Hg.cm-1.sec (p<0.001). CONCLUSION: hMVRI was a strong predictor of long-term MACEs in patients with STEMI treated with primary PCI.

Efficacy of Combination Treatment with Intracoronary Abciximab and Aspiration Thrombectomy on Myocardial Perfusion in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Coronary Stenting

PURPOSE: We aimed to investigate whether combination therapy using intracoronary (IC) abciximab and aspiration thrombectomy (AT) enhances myocardial perfusion compared to each treatment alone in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We enrolled 40 patients with STEMI, who presented within 6 h of symptom onset and had Thrombolysis in MI flow 0/1 or a large angiographic thrombus burden (grade 3/4). Patients were randomly divided into 3 groups: 10 patients who received a bolus of IC abciximab (0.25 mg/kg); 10 patients who received only AT; and 20 patients who received both treatments. The index of microcirculatory resistance (IMR) was measured with a pressure sensor/thermistor-tipped guidewire following successful PCI. Microvascular obstruction (MVO) was assessed using cardiac magnetic resonance imaging on day 5. RESULTS: IMR was lower in the combination group than in the IC abciximab group (23.5+/-7.4 U vs. 66.9+/-48.7 U, p=0.001) and tended to be lower than in the AT group, with barely missed significance (23.5+/-7.4 U vs. 37.2+/-26.1 U, p=0.07). MVO was observed less frequently in the combination group than in the IC abciximab group (18.8% vs. 88.9%, p=0.002) and tended to occur less frequently than in the AT group (18.8% vs. 66.7%, p=0.054). No difference of IMR and MVO was found between the IC abciximab and the AT group (66.9+/-48.7 U vs. 37.2+/-26.1 U, p=0.451 for IMR; 88.9% vs. 66.7%, p=0.525 for MVO, respectively). CONCLUSION: Combination treatment using IC abciximab and AT may synergistically improve myocardial perfusion in patients with STEMI undergoing primary PCI (Trial Registration: clinicaltrials. gov Identifier: NCT01404507).

Genotype- and Phenotype-Directed Personalization of Antiplatelet Treatment in Patients with Non-ST Elevation Acute Coronary Syndromes Undergoing Coronary Stenting

BACKGROUND AND OBJECTIVES: We evaluated the effectiveness of genotype- and phenotype-directed individualization of P2Y12 inhibitors to decrease high on-treatment platelet reactivity (HOPR). SUBJECTS AND METHODS: Sixty-five patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes were randomly assigned to genotype- or phenotype-directed treatment. All patients were screened for CYP2C19*2, *3, or *17 alleles by using the Verigene CLO assay (Nanosphere, Northbrook, IL, USA). The P2Y12 reaction unit (PRU) was measured using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). 21 CYP2C19 *2 or *3 carriers (65.6%) and 11 patients with HOPR (33.3%), defined as a PRU value > or =230, were given 90 mg ticagrelor twice daily; non-carriers and patients without HOPR were given 75 mg clopidogrel daily. The primary endpoint was the percentage of patients with HOPR after 30 days of treatment. RESULTS: PRU decreased following both genotype- and phenotype-directed therapies (242+/-83 vs. 109+/-90, p<0.001 in the genotype-directed group; 216+/-74 vs. 109+/-90, p=0.001 in the phenotype-directed group). Five subjects (16.2%) in the genotype-directed group and one (3.3%) in the phenotype-directed group had HOPR at day 30 (p=0.086). All patients with HOPR at the baseline who received ticagrelor had a PRU value of <230 after 30 days of treatment. Conversely, clopidogrel did not lower the number of patients with HOPR at the baseline. CONCLUSION: Tailored antiplatelet therapy according to point-of-care genetic and phenotypic testing may be effective in decreasing HOPR after 30 days.

Health-Related Quality-of-Life after Percutaneous Coronary Intervention in Patients with UA/NSTEMI and STEMI: the Korean Multicenter Registry

Compared with ST elevation myocardial infarction (STEMI), long-term outcomes are known to be worse in patients with unstable angina/non-STEMI (UA/NSTEMI), which might be related to the worse health status of patients with UA/STEMI. In patients with UA/NSTEMI and STEMI underwent percutaneous coronary intervention (PCI), angina-specific and general health-related quality-of-life (HRQOL) was investigated at baseline and at 30 days after PCI. Patients with UA/NSTEMI were older and had higher frequencies in female, diabetes and hypertension. After PCI, both angina-specific and general HRQOL scores were improved, but improvement was much more frequent in angina-related HRQOL of patients with UA/NSTEMI than those with STEMI (44.2% vs 36.8%, P < 0.001). Improvement was less common in general HRQOL. At 30-days after PCI, angina-specific HRQOL of the patients with UA/NSTEMI was comparable to those with STEMI (56.1 +/- 18.6 vs 56.6 +/- 18.7, P = 0.521), but general HRQOL was significantly lower (0.86 +/- 0.21 vs 0.89 +/- 0.17, P = 0.001) after adjusting baseline characteristics (P < 0.001). In conclusion, the general health status of those with UA/NSTEMI was not good even after optimal PCI. In addition to angina-specific therapy, comprehensive supportive care would be needed to improve the general health status of acute coronary syndrome survivors.

Trans-Radial versus Trans-Femoral Intervention for the Treatment of Coronary Bifurcations: Results from Coronary Bifurcation Stenting Registry

Trans-radial (TR) approach is increasingly recognized as an alternative to the routine use of trans-femoral (TF) approach. However, there are limited data comparing the outcomes of these two approaches for the treatment of coronary bifurcation lesions. We evaluated outcomes of TR and TF percutaneous coronary interventions (PCI) in this complex lesion. Procedural outcomes and clinical events were compared in 1,668 patients who underwent PCI for non-left main bifurcation lesions, according to the vascular approach, either TR (n = 503) or TF (n = 1,165). The primary outcome was major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) in all patients and in 424 propensity-score matched pairs of patients. There were no significant differences between TR and TF approaches for procedural success in the main vessel (99.6% vs 98.6%, P = 0.08) and side branches (62.6% vs 66.7%, P = 0.11). Over a mean follow-up of 22 months, cardiac death or MI (1.8% vs 2.2%, P = 0.45), TLR (4.0% vs 5.2%, P = 0.22), and MACE (5.2% vs 7.0%, P = 0.11) did not significantly differ between TR and TF groups, respectively. These results were consistent after propensity score-matched analysis. In conclusion, TR PCI is a feasible alternative approach to conventional TF approaches for bifurcation PCI (clinicaltrials.gov number: NCT00851526).

Impact of Arterial Stiffness on Regional Myocardial Function Assessed by Speckle Tracking Echocardiography in Patients with Hypertension

BACKGROUND: Arterial stiffening may affect regional myocardial function in hypertensive patients with normal ejection fraction (EF). METHODS: Brachial-ankle pulse wave velocity (PWV) was measured in 70 patients, of mean age 48 +/- 14 years, with untreated hypertension and EF > 55%. Using two-dimensional-speckle tracking echocardiography, we measured longitudinal and circumferential strain (epsilon) and strain rate (SR). Basal and apical rotations were measured using short axis views. RESULTS: The mean systolic and diastolic blood pressure in these patients was 152 +/- 15 mmHg and 92 +/- 11 mmHg, respectively. The mean value of PWV was 1578 +/- 274 cm/s. PWV significantly correlated with age (r = 0.682, p 1700 cm/s compared to those with PWV < or = 1400 cm/s or those with PWV 1400-1700 cm/s. CONCLUSION: In hypertensive patients with normal ejection fraction, arterial stiffening contributes to impaired systolic and diastolic function of the regional myocardium. Compensatory increases in ventricular twist were diminished in patients with advanced stage of vascular stiffening.

Rho-Associated Kinase 2 Polymorphism in Patients With Vasospastic Angina

BACKGROUND AND OBJECTIVES: Recent studies indicate that in response to vasoconstrictor stimuli, the small GTPase RhoA and its down-stream effector, Rho-associated kinase 2 (ROCK)/Rho-kinase, are associated with hypercontraction of the vascular smooth muscle of coronary arteries through augmentation of myosin light chain phosphorylation and Ca2+ sensitization. Expression of ROCK/Rho-kinase mRNA was significantly increased and up-regulated in the spastic coronary artery in a porcine model, and a specific inhibitor of ROCK/Rho-kinase inhibited coronary artery spasm in humans. We therefore explored the role of ROCK2 polymorphisms in the pathogenesis of vasospastic angina (VA). SUBJECTS AND METHODS: We studied 106 patients with VA who exhibited spontaneous or provoked coronary spasm during coronary angiography and compared the prevalence of ROCK2 polymorphisms between this group of patients with VA and controls whose angiograms were normal, and in whom the ergonovine test did not cause spasm (n=107). Five single nucleotide polymorphisms (SNPs) of the ROCK2 gene were selected. SNPs were genotyped by high-resolution melting. Linkage disequilibrium and haplotype analyses were performed using the SHEsis program. RESULTS: The prevalence of genotypes of the 5 interesting SNPs in patients with VA was not different from that in the control group. In haplotype analysis, the haplotype G-T-C-T-G (in order of rs978906, rs2271621, rs2230774, rs1515210, and rs3771106) was significantly associated with a decreased risk of VA (p=0.007). CONCLUSION: The haplotype G-T-C-T-G in the ROCK2 gene had a protective effect against VA, suggesting the involvement of ROCK2 in VA pathogenesis.